The family of Bcl-2 proteins plays pivotal roles in either promoting or preventing apoptosis. Bcl-2 family members contain one or more of four characteristic Bcl-2 homology (BH) domains, which are crucial for function. For example, anti-apoptotic Bcl-2 family proteins prevent death signaling by heterodimerizing with pro-death proteins at their BH3 domains. ABT-263 is a potent, orally bioavailable mimetic of BH3 domains that avidly binds Bcl-2, Bcl-XL, and Bcl-W (Ki < 1 nM for all three proteins). It blocks the interaction of these proteins with pro-death proteins, like Bim, leading to apoptosis. ABT-263, alone, can induce regression of some tumors in some xenograft mouse models of cancer. It can also potentiate the therapeutic efficacy of chemotherapeutic compounds. Interestingly, ABT-263 induces apoptosis in cancer cell lines expressing mutants of β-catenin a Wnt signaling factor commonly mutated in a range of cancer types.